Disruptions of emotional information processing (e.g., attention to, memory for, and interpretation of emotional information) have been implicated in depression. The emerging field of affective neuroscience suggests there are distinct physiological correlates of emotional information processing styles. The proposed research integrates basic research on affective neuroscience with conclusions from cognitive-clinical research regarding depressive information processing to understand brain mechanisms associated with disruptions of emotional information processing in depression. The applicant, Dr. Greg Siegle, Ph.D., has examined information processing in depressive disorders for eight years, and has developed a computational neural network model that suggests a convergence of specific cognitive, environmental, and biological factors are associated with depression. Further training is necessary for the next step in this research, which involves clearly linking observed cognitive phenomena and model behaviors to underlying biological mechanisms. Short-term goals include using cognitive, physiological, and neuroimaging assessment to test predictions, generated using the model, regarding interactions of factors that could lead to distinct profiles of depressive emotional information processing. Long-term goals involve using this research to direct depressed individuals to focused treatments that target their particular cognitive and physiological profiles, thus improving speed and efficacy of depression interventions. The proposed research involves assessing depressed individuals' pupil dilation and brain activity (via functional magnetic resonance imaging; fMRI) during emotional information processing tasks to create profiles of emotional information processing disruptions in depression. Computational neural network modeling of interactions between relevant brain structures will be used to generate and refme hypotheses and experimental design throughout the study. This research will allow development and refinement of a formal theory of psychobiological mechanisms underlying individual differences in depressive information processing biases. It will lead to an R01 proposal involving understanding changes in brain activity associated with treatment for depression. Research will be conducted at the Western Psychiatric Institute and Clinic, a world center for research on the psychobiology of depression. Researchers who are expert in depression as well as the proposed assessment technologies will serve as mentors and preceptors.